The Comparative Effectiveness and Safety of Pharmacotherapies for the Treatment of Opioid Use Disorder in Pregnancy

治疗妊娠期阿片类药物使用障碍的药物疗法的有效性和安全性比较

• 批准号: 10319626
• 负责人: Brian Thomas Bateman
• 金额: $ 68.81万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10319626
• 关键词: Affinity; Agonist; Buprenorphine; Cesarean section; Child; Clinical; Congenital Abnormality; Data; Ensure; Epidemiologic Methods; Formulation; Frequencies; General Population; Goals; Guidelines; Injections; International; Low Birth Weight Infant; Measures; Medicaid; Medical Societies; Methadone; Methods; Mothers; Naloxone; Neonatal Abstinence Syndrome; Neurodevelopmental Disorder; Observational Study; Opioid Antagonist; Outcome; Patient Selection; Personal Satisfaction; Pharmaceutical Preparations; Pharmacology; Pharmacotherapy; Postpartum Period; Pregnancy; Pregnancy Outcome; Pregnant Women; Premature Birth; Prenatal care; Prevalence; Public Health; Randomized Controlled Trials; Recommendation; Relative Risks; Research; Residual state; Risk; Safety; Small for Gestational Age Infant; Stratification; Suboxone; United States National Institutes of Health; Withdrawal Symptom; Woman; adverse outcome; adverse pregnancy outcome; base; beneficiary; buprenorphine treatment; cohort; comparative; comparative effectiveness; comparative safety; congenital anomaly; design; effectiveness outcome; fetal; high dimensionality; high risk; high risk population; illicit opioid; improved; interest; maternal risk; mu opioid receptors; neonatal outcome; neonate; neurodevelopment; opioid agonist therapy; opioid treatment program; opioid use; opioid use disorder; opioid withdrawal; prevent; retention rate; safety outcomes; severe maternal morbidity; social; substance use; treatment comparison

ABSTRACT The frequency of opioid use disorders (OUD) during pregnancy has increased substantially during the past two decades, reflecting the risk observed in the general population. The current recommendation from guideline groups is that pregnant women with OUD be treated with opioid agonist therapy (OAT). OAT has been shown to improve pregnancy outcomes in women with OUD because it prevents opioid withdrawal symptoms that can be disruptive to fetal well-being and to reduce illicit opioid and other substance use. Methadone has historically been the mainstay of OUD treatment during pregnancy. However, in recent years, buprenorphine use has increased and is now used in approximately equal measure with methadone. Methadone and buprenorphine have different pharmacologic effects. The way in which these treatments are administered is also different. Methadone is dispensed under observation via a federally- regulated opioid treatment program. In contrast, buprenorphine is generally dispensed by prescription in a routine office-based setting. Buprenorphine also comes in two formulations, as a monoproduct and in combination with naloxone, an opioid antagonist, which is intended to deter misuse via injection. Comparative safety and effectiveness data for pharmacologic approaches to the treatment of OUD in pregnancy are very limited. The MOTHER trial demonstrated that buprenorphine is associated with less severe neonatal abstinence syndrome compared to methadone. Data regarding the comparative safety of buprenorphine and methadone with respect to other adverse pregnancy outcomes and the impact on long-term neurodevelopment are few and subject to a number of potential biases and limitations. The comparative effectiveness of buprenorphine and methadone with respect to retention in treatment and impact on adequacy of prenatal care has also not been fully defined. For those prescribed buprenorphine in pregnancy, the use of the monoproduct is generally recommended, despite the higher risk for misuse, because there are few data regarding the safety of the combination product which includes naloxone. The overall goal of this study is to utilize state of the art design and analytic epidemiological methods applied to a large cohort of women defined using nationwide Medicaid data to generate the best possible evidence regarding the comparative safety and effectiveness of medications used to treat OUD in pregnancy. Specific methods that we intend to employ include propensity score fine stratification, high-dimensional propensity score adjustment, alternative referents (discontinuer comparisons), and bias analyses to account for potential misclassification of exposure and outcome and residual confounding. The results of the studies are expected to have an important and direct clinical impact guiding clinicians’ and patients’ selection of the best treatment for OUD in order to ensure a good outcome for mothers and their children.

摘要 怀孕期间阿片类药物使用障碍(OUD)的频率在 过去二十年，反映了在普通人群中观察到的风险。目前的建议来自 指导原则是对患有UD的孕妇进行阿片激动剂治疗(OAT)。燕麦有 已被证明可以改善患有OUD的妇女的妊娠结局，因为它可以防止阿片类药物的戒断 可能会破坏胎儿健康的症状，并减少非法阿片类药物和其他物质的使用。 美沙酮历来是怀孕期间OUD治疗的主要药物。然而，近年来， 丁丙诺啡的使用量有所增加，现在与美沙酮的使用量大致相当。 美沙酮和丁丙诺啡具有不同的药理作用。它们以何种方式 治疗方法也是不同的。美沙酮是在观察下通过联邦- 规范的阿片类药物治疗计划。相比之下，丁丙诺啡通常以处方形式在 日常办公环境。丁丙诺啡也有两种剂型，一种是单药，另一种是 与阿片类拮抗剂纳洛酮联合使用，旨在通过注射阻止滥用。比较 药物治疗妊娠期胎儿窘迫综合征的安全性和有效性数据非常多。 有限的。母亲试验表明丁丙诺啡与病情较轻的新生儿相关。 戒断综合症与美沙酮的比较。关于丁丙诺啡和丁丙诺啡相对安全性的数据 美沙酮与其他不良妊娠结局的关系及其对长期神经发育的影响 数量很少，并受到一些潜在的偏见和限制。两种方法的相对有效性 丁丙诺啡和美沙酮在治疗中的滞留及其对产前护理充分性的影响 也没有得到充分的定义。对于那些在怀孕期间开出丁丙诺啡处方的人，使用单品 尽管误用风险较高，但通常建议使用，因为关于安全性的数据很少 包括纳洛酮的联合产品。 这项研究的总体目标是利用最先进的设计和分析流行病学方法 应用于使用全国医疗补助数据定义的一大批女性，以产生尽可能好的 关于用于治疗妊娠期胎儿窘迫的药物的相对安全性和有效性的证据。 我们打算采用的具体方法包括倾向评分精细分层、高维 倾向分数调整、替代参照物(不连续者比较)和偏见分析以说明 可能会对暴露和结果进行错误分类，并造成残留混淆。研究结果如下： 预计将对临床医生和患者的择优选择产生重要和直接的临床影响 为了确保母亲和她们的孩子有一个好的结局，我们必须对其进行积极的治疗。